The overall goal of this proposal is to investigate the potential for in-vivo guided cancer therapies using the multi-modal imaging approach in pre-clinical animal models of human cancer. With the advances in cancer treatments, both chemotherapeutic and genetic, it becomes crucial to be able to determine their efficacy, which is crucial for overall patient survival. Non-invasive imaging techniques are currently available for visualizing different pathological conditions of the human body, but their use for cancer monitoring is limited due to the lack of tumor-specific imaging probes. We have recently developed a multi-modal imaging probe targeting the underglycosylated mucin-1 tumor antigen (uMUC-1), which is one of the early hallmarks of tumorigenesis in a wide variety of tumors. Our tumor-specific multi-modal imaging probe consists of crosslinked superparamagnetic iron oxide nanopartides (CLIO) for MR imaging, modified with Cy5.5 dye (for optical near-infrared imaging, NIRF), and has peptides, specifically recognizing uMUC-1, attached to its dextran coat. MUC-1 is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas, including more than 90% of human breast cancers, pancreatic, colorectal, lung, prostate, and gastric carcinomas. Moreover, uMUC-1 expression has been demonstrated in non-epithelial cancer cell- lines, as well as in hematological malignancies, such as multiple myeloma and some B-cell non-Hodgkin lymphomas. In this application we propose to investigate the possibility of non-invasive monitoring of treatment-related changes in tumor progression/regression using conventional chemotherapeutic agents as well as novel approaches such as siRNA technology. We will also evaluate changes in tumor volume, which can be detected using the CLIO-EPPT probe and compare our findings using this probe with conventional dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with Gadolinium-DTPA (Gd-DTPA).We will evaluate uMUC-1 expression during the course of chemotherapy and correlate it with CLIO-EPPT accumulation. If successful, this study can further be translated into clinical applications, since related iron oxides have already been tested in clinical trials. [unreadable] [unreadable] [unreadable]